The management of prosthetic joint infections (PJIs) poses significant challenges, requiring a multidisciplinary approach involving surgical, microbiological, and pharmacological expertise. Suppressive antibiotic therapy (SAT) has emerged as a viable option in cases where curative interventions are deemed unfeasible. This review provides an updated synthesis of recent evidence on SAT, including its indications, efficacy, practical considerations, and associated challenges. We aim to highlight the nuances of this therapeutic approach, discuss the factors influencing its success, and offer future directions for research to optimize patient outcomes.

Background/Objectives: The optimal duration of antibiotic therapy for bacterial prosthetic joint infections (PJI) remains a topic of considerable debate. Current recommendations are often based on limited evidence and expert consensus. Emerging data suggest that shorter antibiotic courses may be as effective as prolonged treatments in select cases. Shortening the duration of therapy offers several advantages, including a reduced risk of bacterial resistance, fewer adverse events, and cost savings. However, this approach must be carefully balanced with the individual patient’s risk of treatment failure. This narrative review aims to synthesize current evidence regarding the duration of antibiotic therapy in PJIs, according to surgical strategies—DAIR (debridement, antibiotics, and implant retention), one-stage exchange, two-stage exchange, and resection without reimplantation—and to identify parameters that may guide individualized and potentially shortened regimens. Methods: We conducted a comprehensive search of PubMed, Embase, and Cochrane Library databases through January 2025, including observational studies, randomized controlled trials, and international guidelines. Reference lists of key articles were also screened. Results: Studies on DAIR suggest that longer regimens (e.g., 8–12 weeks) are necessary, especially in staphylococcal infections, as confirmed by the DATIPO trial, which showed higher failure rates with 6 weeks compared to 12 weeks. Evidence on one-stage exchange is limited but increasingly suggests that 6 weeks may be sufficient in selected patients; however, no dedicated trial has confirmed this. In two-stage exchange, small retrospective series report successful outcomes with short antibiotic therapy combined with local antibiotics, but randomized trials show trends favoring longer regimens. For patients treated with permanent resection arthroplasty, arthrodesis, or amputation, antibiotic durations are highly variable, with few robust data. Across all strategies, most studies are limited by methodological weaknesses, including small sample sizes, retrospective design, lack of microbiological stratification, and heterogeneous outcome definitions. Conclusions: Despite growing interest in shortening antibiotic durations in PJIs, high-quality evidence remains limited. Until additional randomized trials are available—particularly in one- and two-stage exchange settings—12 weeks remains the safest reference duration for most patients, especially those with retained hardware. Future studies should incorporate stratification by infection type, causative organism, and host factors to define tailored and evidence-based antibiotic strategies.

The management of prosthetic joint infections (PJIs) poses significant challenges, requiring a multidisciplinary approach involving surgical, microbiological, and pharmacological expertise. Suppressive antibiotic therapy (SAT) has emerged as a viable option in cases where curative interventions are deemed unfeasible. This review provides an updated synthesis of recent evidence on SAT, including its indications, efficacy, practical considerations, and associated challenges. We aim to highlight the nuances of this therapeutic approach, discuss the factors influencing its success, and propose future directions for research to optimize patient outcomes.

Background/Objectives: The optimal duration of antibiotic therapy, a cornerstone of PJI treatment, remains a topic of considerable debate, with current recommendations often based on limited evidence and expert consensus. Emerging evidence suggests that shorter antibiotic courses may be as effective as prolonged therapies in select cases, provided thorough surgical debridement is performed and biofilm-active agents are used. We aimed to synthesize available data on antibiotic therapy duration based on the surgical technique, along with recall of definitions, diagnosis criteria and classification. Future perspectives on PJI diagnosis have been also presented. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), databases were searched using predefined medical subject headings (MeSH) and PUBMED. Randomized controlled trials (RCTs), observational studies, and expert guidelines have been synthetized. Results: A total of 2305 articles involving observational studies and randomized controlled trials were reviewed. We summarized the results of studies that have compared shorter antibiotic courses to prolonged therapies according to the surgical procedure. Forty five studies were analyzed. Definitions and classification of PJI were mentioned for a better analysis. Future perspectives were also noted. Conclusions: This review highlights the limited data available for evaluating antibiotic duration in the setting of PJI. The most studies found that a shorter antibiotic duration was non-inferior to a longer duration in selected cases but evidence-based guidelines to harmonize practices and improve outcomes for PJI patients are needed.